There was one second left in the sixth round of Saturday’s big fight in Vegas between Manny Pacquiao and Juan Manuel Márquez. Pacquiao, one of the best boxers in the world, had been picking apart his old nemesis Márquez with darty punches that the Mexican, an expert counterpuncher, couldn’t seem to counter. The Filipino fighter had connected on 94 punches to Márquez’s 52, had broken his opponent’s nose and dropped him in the previous round. Márquez was bleeding profusely and having trouble breathing. All three judges had Pacquiao winning 47–46 through five rounds.

Then in the dying moments of round six, the two men started exchanging furious punches near the ropes. Márquez feinted left and threw one of the most vicious short rights in recent boxing history, hitting Pacquiao flush in the face and sending him to the canvas, right in front of Mitt and Ann Romney’s ringside seats (“I couldn’t believe it, he went down right in front of me!” Ann said later). It seemed oddly appropriate: Romney knows all about clear defeats emerging dramatically after close and tough battles. And Pacquiao is a politician — a Congressman with presidential ambitions in his native Philippines.

There was exaltation from Márquez, all sprinkled with blood, from his cornermen and from the mostly pro-Márquez crowd at the MGM Grand. But the obvious end of the match was also chilling because Pacquiao, seemingly invincible once upon a time, was so slow to revive. His corner put a white wet towel over him and started massaging his head as his weeping wife Jinkee — whose name is tattooed on his arm — struggled into the ring and to his side. Eventually regaining consciousness, Pacquiao said, “I got hit by a punch I didn’t see.” His eyes were still glazed over.

It felt like the end of Manny Pacquaio. This is the second fight he has lost this year. Despite his dominance over Márquez through most of the fight, he looked just slightly more timid than the Pacquiao of old; his legs didn’t move along with their typical bounce; he had been knocked down in round three, the first time that had happened in years and an omen for the way the struggling Márquez would finish the match. One of the smartest men in boxing, Márquez was setting up his KO.

The punch that ended the fight would bring a resounding conclusion to one of the bitterest rivalries in sports. Until Saturday, Márquez could claim to have been cheated by history. Considered the sixth best pound-for-pound boxer in the world, he fought Pacquiao to a controversial draw in 2004; he then lost a split decision (by one point) in their 2008 rematch. Márquez again lost to Pacquiao in a 2011 controversy. At the conclusion of that fight, when the judges ruled that Pacquiao had won, the Filipino was greeted by thunderous boos. Márquez, disgusted, stormed out of the ring, believing he had won. He would prove he deserved victory by knockout at the end of round six of their fourth encounter — one of the most exciting in recent years, an instant classic.

It might not have happened. After their 2011 match, Pacquiao was moving onto younger fighters and bigger paydays, and maybe — just maybe — an eventual superfight with Floyd Mayweather Jr.

But earlier this year Pacquiao lost a controversial decision to Timothy Bradley. While Pacquiao lost on the judges’ scorecards, the boxing public believed he had soundly beaten Bradley — who was wheeled into the postfight press conference in a wheelchair. But since Mayweather’s and Pacquiao’s promoters never seem able to negotiate their fight for various reasons — most being nonsensical — Pacquiao decided to take on Márquez again. And as the Filipino’s coach Freddie Roach says, “He walked into a two-inch punch.” Pacquiao hadn’t been knocked out since 1999.

He might retire. He might fight Márquez for a fifth time. But what is clear: that punch will permanently alter the way Pacquiao is viewed as a boxer, politician and cross-cultural star.

As a fighter, he relied on his speed to create punching angles and then quickly move out of range of his opponent. But as he aged, he wasn’t quite getting out of counterattacks as much. In training camp, there was talk of Pacquiao knocking out his sparring partners, but other, quieter stories of missed training runs and a lack of dedication to his strength and fitness regime. To many who know him well, he seemed more interested in Bible study than the sweet science. There were also uneasy questions from his own countryman about his dedication to the Philippines’ fervent Catholicism, sensing a turn toward evangelical born-again Protestantism. Indeed, there were some snarky tweets that his defeat may have been the result of not performing what had seemed to be a prefight ritual: kneeling in a corner and making the Catholic sign of the cross. Pacquiao seems to be writing a different — more complex — storyline to his life, and it hasn’t been easy for his countrymen to digest. And the latest loss may shake the faith of his many non-Filipino fans who have made him a global brand — but one based on winning and invincibility.

After the fight, Pacquiao readily confessed to overconfidence, believing the bloodied Márquez to be on his last legs. However, Roach, himself an icon of perseverance because of his public struggle with Parkinson’s, said that though Pacquiao looked careless at times, the end is not nigh. “If I see signs of him declining, I will tell him to retire. I don’t think this is the end of Manny Pacquiao, no.” It was simply a mistake. He did not see the punch coming. That says a lot for Pacquiao’s vision. In Márquez’s view, he had it coming.